Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objectives:To explore the value of non-invasive myocardial work combined with myocardial contrast echocardiography(MCE)in the early diagnosis of coronary artery disease and its efficacy in stratifying the severity of coronary vessel lesions.Methods:A total of 130 patients with suspected coronary artery disease admitted to the First Affiliated Hospital of Dalian Medical University from June 2024 to January 2025 were enrolled in this study.All patients underwent echocardiography and MCE after admission,and coronary angiography(CAG).Based on CAG results,patients were divided into non-CAD group(n=45,coronary artery stenosis<50%)and CAD group(n=85,coronary artery stenosis≥50%).Patients in CAD group were further divided into low-score CAD group(≤49 points,n=43)and high-score CAD group(>49 points,n=42)according to the median of Gensini score(49 points).Non-invasive MW indices and quantitative MCE parameters were assessed.A binary logistic regression model was used to construct a combined diagnostic model,and the value of each parameter in diagnosing CAD and evaluating the severity of coronary lesions was calculated.The receiver operating characteristic(ROC)curve of subjects was estimated,and the area under the curve(AUC)was calculated to evaluate its sensitivity and specificity for early diagnosis of coronary heart disease.Results:Compared with the non-CAD group,the global longitudinal strain,global work index(GWI),and global constructive work(GCW)in both low-score and high-score CAD groups were significantly lower(all P<0.05),and the global work efficiency in the high-score CAD group was significantly reduced(P<0.05).MCE indices in both low-score and high-score CAD groups were significantly lower than those in the non-CAD group(all P<0.05).The multivariate logistic stepwise regression analysis and ROC curve showed that GWI(OR=0.997,95%CI:0.995-0.999,P=0.003)and A value(representing the peak intensity of the curve,reflecting myocardial blood volume(OR=0.415,95%CI:0.246-0.698,P=0.001)were independent predictors of low-score CAD.The combined diagnostic sensitivity and specificity for low-score coronary artery disease were 72.1%and 88.9%respectively,with an AUC of 0.851.GCW(OR=0.997,95%CI:0.995-1.000,P=0.019)and β-value(OR=0.000,95%CI:0.000-0.003,P<0.001)were independent predictors of high-score CAD.The combined diagnostic sensitivity and specificity for high-score coronary artery disease were 88.1%and 88.9%respectively,with an AUC of 0.934.Conclusions:Both non-invasive myocardial work parameters and MCE parameters have high diagnostic efficacy for coronary artery lesions of various degrees.The combined application of the two methods significantly improves the accuracy of coronary artery disease diagnosis,with improved sensitivity and specificity than single technique.Our results provide a new non-invasive comprehensive diagnostic model for clinical early diagnosis and risk stratification of coronary artery disease.

Objectives:To explore the value of non-invasive myocardial work combined with myocardial contrast echocardiography(MCE)in the early diagnosis of coronary artery disease and its efficacy in stratifying the severity of coronary vessel lesions.Methods:A total of 130 patients with suspected coronary artery disease admitted to the First Affiliated Hospital of Dalian Medical University from June 2024 to January 2025 were enrolled in this study.All patients underwent echocardiography and MCE after admission,and coronary angiography(CAG).Based on CAG results,patients were divided into non-CAD group(n=45,coronary artery stenosis<50%)and CAD group(n=85,coronary artery stenosis≥50%).Patients in CAD group were further divided into low-score CAD group(≤49 points,n=43)and high-score CAD group(>49 points,n=42)according to the median of Gensini score(49 points).Non-invasive MW indices and quantitative MCE parameters were assessed.A binary logistic regression model was used to construct a combined diagnostic model,and the value of each parameter in diagnosing CAD and evaluating the severity of coronary lesions was calculated.The receiver operating characteristic(ROC)curve of subjects was estimated,and the area under the curve(AUC)was calculated to evaluate its sensitivity and specificity for early diagnosis of coronary heart disease.Results:Compared with the non-CAD group,the global longitudinal strain,global work index(GWI),and global constructive work(GCW)in both low-score and high-score CAD groups were significantly lower(all P<0.05),and the global work efficiency in the high-score CAD group was significantly reduced(P<0.05).MCE indices in both low-score and high-score CAD groups were significantly lower than those in the non-CAD group(all P<0.05).The multivariate logistic stepwise regression analysis and ROC curve showed that GWI(OR=0.997,95%CI:0.995-0.999,P=0.003)and A value(representing the peak intensity of the curve,reflecting myocardial blood volume(OR=0.415,95%CI:0.246-0.698,P=0.001)were independent predictors of low-score CAD.The combined diagnostic sensitivity and specificity for low-score coronary artery disease were 72.1%and 88.9%respectively,with an AUC of 0.851.GCW(OR=0.997,95%CI:0.995-1.000,P=0.019)and β-value(OR=0.000,95%CI:0.000-0.003,P<0.001)were independent predictors of high-score CAD.The combined diagnostic sensitivity and specificity for high-score coronary artery disease were 88.1%and 88.9%respectively,with an AUC of 0.934.Conclusions:Both non-invasive myocardial work parameters and MCE parameters have high diagnostic efficacy for coronary artery lesions of various degrees.The combined application of the two methods significantly improves the accuracy of coronary artery disease diagnosis,with improved sensitivity and specificity than single technique.Our results provide a new non-invasive comprehensive diagnostic model for clinical early diagnosis and risk stratification of coronary artery disease.

OBJECTIVE To explore the pathogens isolated from the patients with oral and maxillofacial space infec-tions and the expressions of inflammatory factors and analyze their significance so as to provide bases for treatment of the disease.METHODS The clinical data were collected from 186 patients with oral and maxillofacial space in-fections who were treated in the Second Hospital of Shanxi Medical University from Dec.2019 to May 2024.The secretions were collected from the infection sites.Pathogens were identified,the drug susceptibility testing was performed,and the infection sites were analyzed.The biofilm formation ability was evaluated by crystal violet stai-ning method.The levels of serum D-Dimer,high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),procalcitonin(PCT)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay.The human oral epithelial cells(HOEC)were cultured,the adhesion and invasion abilities and release of the induced inflammatory factors of Staphylococcus aureus and Streptococcus constellatus strains were evaluated.RESULTS The single-space infection was the predominant type of the oral and maxillofacial space infec-tions and mainly caused by gram-positive bacteria.The infections resulted in the rise of serum inflammatory fac-tors(D-Dimer,hs-CRP,PCT,TNF-α and IL-6).The S.aureus and S.constellatus strains showed strong adhe-sion and invasion abilities to HOEC,which may induce the secretion of large amount of inflammatory factors;the S.aureus strains presented higher pathogenicity and inflammation-induced ability.CONCLUSIONS The single-space infection caused by the gram-positive bacteria is dominant among the oral and maxillofacial space infections.The S.aureus strains mediate the progress of infections through intensifying the cellular adhesion,in-vasion and intracellular survival mechanisms.

OBJECTIVE To explore the pathogens isolated from the patients with oral and maxillofacial space infec-tions and the expressions of inflammatory factors and analyze their significance so as to provide bases for treatment of the disease.METHODS The clinical data were collected from 186 patients with oral and maxillofacial space in-fections who were treated in the Second Hospital of Shanxi Medical University from Dec.2019 to May 2024.The secretions were collected from the infection sites.Pathogens were identified,the drug susceptibility testing was performed,and the infection sites were analyzed.The biofilm formation ability was evaluated by crystal violet stai-ning method.The levels of serum D-Dimer,high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),procalcitonin(PCT)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay.The human oral epithelial cells(HOEC)were cultured,the adhesion and invasion abilities and release of the induced inflammatory factors of Staphylococcus aureus and Streptococcus constellatus strains were evaluated.RESULTS The single-space infection was the predominant type of the oral and maxillofacial space infec-tions and mainly caused by gram-positive bacteria.The infections resulted in the rise of serum inflammatory fac-tors(D-Dimer,hs-CRP,PCT,TNF-α and IL-6).The S.aureus and S.constellatus strains showed strong adhe-sion and invasion abilities to HOEC,which may induce the secretion of large amount of inflammatory factors;the S.aureus strains presented higher pathogenicity and inflammation-induced ability.CONCLUSIONS The single-space infection caused by the gram-positive bacteria is dominant among the oral and maxillofacial space infections.The S.aureus strains mediate the progress of infections through intensifying the cellular adhesion,in-vasion and intracellular survival mechanisms.

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

The mandibular metastatic spread of carcinoma from the thyroid gland is exceedingly rare. Follicular thyroid carcinoma is the second most common type of thyroid carcinoma，accounting for approximately 10% to 15% of all thyroid cancers. The prognosis of FTC is relatively satisfactory. Due to its rich blood transport, it is easy to metastasize hematological, with the main sites of metastasis are bone and lung. However，mandibular metastasis of thyroid follicular carcinoma is rare. We report a case of thyroid follicular carcinoma that metastasized to the ascending ramus of the mandible 21 years after surgery.The operation was successfully completed, and there was no recurrence during postoperative follow-up. Due to the absence of obvious clinical symptoms in the patient, the diagnosis and treatment were challenging. We have provided detailed radiographic and pathological images to facilitate understanding and discussion of the disease.
Humans ; Adenocarcinoma, Follicular/pathology* ; Thyroid Neoplasms/surgery* ; Prognosis ; Mandible

Objective:To understand the user experience of Nursing-Online Practice Promotion Application ("N-OPP" APP) .Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 537 nursing students who had practiced in the Affiliated Hospital of Qingdao University from August to November 2020 and had used "N-OPP" APP were selected as the research objects. The general data questionnaire and the "N-OPP" APP user experience evaluation questionnaire were used for the investigation. A total of 537 questionnaires were distributed in this study and 529 valid questionnaires were recovered, with an effective recovery rate of 98.51%.Results:The total average score of the "N-OPP" APP user experience evaluation questionnaire items of 529 nursing students was (3.89±0.47) , and the average scores of items of operation performance, service performance, user experience and risk were respectively (3.87±0.65) , (4.04±0.60) , (3.90±0.70) and (3.42±0.62) . There were statistically significant differences in the use experience and operation performance dimensions of nursing students from different educational backgrounds, contact time of mobile learning APP, use time and use frequency of "N-OPP" APP ( P<0.05) . The service performance dimension items of nursing students with different educational background and frequency of "N-OPP" APP were compared, and the differences were statistically significant ( P<0.01) . The risk dimension items of nursing students with different "N-OPP" APP use frequencies were compared, and the difference was statistically significant ( P<0.01) . Conclusions:The development of "N-OPP" APP can solve some problems in the traditional teaching and training of clinical nursing skills, help nursing students to consolidate their nursing skills and obtain high recognition from nursing students, which can be used as an auxiliary tool for teaching and training of clinical nursing skills.

Cloud technology and the Internet of things ( IOT) technology can be used in building the patient-centered critical care medical information platform.The platform could inenable medical staff to efficiently obtain critical care medical information, and raise critical patients′ cure rates. The authors introduced the critical process of rapidly building and improving the urgent care medical information integration platform in a campus of the First Affiliated Hospital of Zhejiang University Medical School.The IOT platform could effectively interconnect a variety of critical care medical equipments, and features such functions as vital signs monitoring and life support, bedside treatment data retrieval, remote diagnosis and treatment, and cloud sharing. The platform featured the advantages of complete information integration, fast construction, and satisfactory system extensibility. It could improve the medical work efficiency, improve the effect of critical care, and reduce the frequency of contact with patients, hence providing references for rapidly establishing a vital care treatment platform for public health events.

Objective To propose a quick and low-cost personalized diabetic foot modeling and insole design scheme, so as to reduce the plantar pressure accurately. Methods The foot model of the patient was constructed by scaling the model with foot feature parameters, to make biomechanical analysis on plantar pressure. By means of numerical mapping model of insole elasticity and plantar pressure, the three-dimensional (3D) personalized insole model with gradient modulus was constructed. The insole was then manufactured via 3D printing technology and used for experimental validation. Results The related mechanical parameters from finite element prediction of the foot model constructed by the scaling modeling method were close to those of the CT reconstructed model, and the maximum error was controlled within 15%. Compared with wearing the normal insole, the peak pressure of the personalized insole was effectively reduced by 20%. The time and economic cost of this simplified design was reduced by approximately 90%. Conclusions The design scheme of the diabetes insole shortens the design cycle, and the personalized insole can effectively and accurately reduce the sole pressure, and reduce the risk of foot ulcer, which provides a technical basis for the promotion of the personalized diabetes insole.